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Hematology (Genetic Blood Disorders (Hemophilia (A and B) both types…
Hematology
Genetic Blood Disorders
Hemophilia
(A and B)
both types are X-linked recessive
Hemophilia example
Notes
:
Hemophilia is X-linked recessive
find prob of sister having the x-link
--> since she has 2 Xs --> 50%
then she has to pass on the x-'link
--> again 50%
prob of having a boy = 50%
Case presentation:
*Sickle Cell Disease
autosomal recessive
Clinical Cases
Clinical Case
Clinical Case
Notes
:
note that
Sickle Cell example 2
Case presentation:
Notes
:
note the gel electro shows the sickle cell HbS is the heaviest
Sickle Cell example
Case presentation:
Notes
:
Sickle cell anemia is a autosomal recessive disorder
recall the Call the Midwife episode with Nick and Chloe where the black family living in Britain, both the father and son always had pains in the knees and joints when they were doing physical activities
the mother was a carrier, but the father had the disease so he was homo recessive
-- thus the mother was a carrier and 50% of their kids will get it
sickle cell hemoglobin = HbS
note that you can be tested for sickle cell anemia by HbS gel electrophoresis
--> HbS moves slower than normal HbA
Hemoglobin C disease and Sickle Cell example
shows that HbC Missense mutation is similar to HbS missense mutation
HbC mutation is even heavier = more neg than HbS on gel electro
Hb C though has mild symptoms
--> splenomegaly / mild anemia
Case presentation:
Notes
:
a disease that is very similar and in a way milder form of Sickle cell anemia is HbC disease
note you can even have a combo of both sickle cell and HbC disease
Notes
:
HbA (beta globulin) --> HbS
missense mutation in the beta globulin
--> missense meaning missensed as wrong AA
G --> V
think of Sickle cell in africa
moving from Ghana to Uganda / Vaganda --> Uganda get Sickle cell disease
Glutamate (HbA / more (-)) --> switched to Valine (HbS / neutral charge)
Gel Electrophoresis
note that on all DNA and protein gel electros
--> DNA and protein start at the (-) end and move to the + end
the valine in HbS causes the HbS to go slower towards the + end
--> making it seem like the HbS is "heavier"
Mutation in Autosomal recessive SCD
point mutation in beta globulin gene
Glutamate --> Valine
--> makes it more positive and move slower
recall that valine has no charge --> more postive
Homoglobin C disease
auto recessive?
missense mutation of beta globulin of Hb
HbC, similar to Hb S of sickle cell anemia
Hemoglobin C disease and Sickle Cell example
shows that HbC Missense mutation is similar to HbS missense mutation
HbC mutation is even heavier = more neg than HbS on gel electro
Hb C though has mild symptoms
--> splenomegaly / mild anemia
Case presentation:
Notes
:
a disease that is very similar and in a way milder form of Sickle cell anemia is HbC disease
note you can even have a combo of both sickle cell and HbC disease
*Hemoglobin
CO2 transport with Hb
most by bicarb and Cl- exchange into the blood
second most = carbaminoHb = bound CO2 to the N terminus of Hb
rest is dissolved in the blood
Different Types of HemoGlobin
Methemoglobin
when ferrous Iron = Fe2 becomes ferric = SICK iron = Fe3
nitrites cause MEthemoglobin
Notes:
note that methemoglobin can't bind O2 well but has normal O2 levels dissolved in the blood
--> thus NORMAL partial pressure of O2 in blood for methemoglobin
Methemoglobin example
Example
:
Notes
:
note that methemoglobin can't bind O2 well but has normal O2 levels dissolved in the blood
--> thus NORMAL partial pressure of O2 in blood for methemoglobin
Erythrocytes
*Heme Synthesis
in the MIGHTY DRACUALA mitochondria of bone marrow and liver
Notes
:
Blood = B6 cofactor pyridoxine for dALA synthase enzyme
MIGHT DracuALA SUCK blood with GLISSENING Teeth
MIGHTY
= mitochondria makes Heme
Dracu - ALA
= d ALA = delta - aminolevulinic acid
SUCKS
= succinyl coA
GLISTENNING
= glycine
--> succinyl coA and glycine both combine in MITO to make dALA then HEME
Will Ferrel as a VAMPIRE DracuALA - K STEW Conan on Twighlight couple breaking up
Will Ferrel
= Fe and Ferochelase --> make HEME
DracuALA
--> Heme inhibits dALA dracuALA synthase
*Coagulation PAthway
bleeding time
APTT = activated partial Thromboplastic Time
PTT = prothrombin Time
High PTT = prothrombin Time
= Extrinsic Pathway problem
Clinical Case
Clinical Case
Notes
:
note that
10
=
(5)
x
2
x
1
3
+
7
EX
trinsic pathway
Less numbers in it --> extrinsic
-->
PT
(
"play tennis outside"
)
-->
warfarin
(
"war is outside"
)
-->
faster
(30 sec)
12
11
1̶0̶
9
(8)
IN
trinsic pathway (= in the blood)
"
MORE
#'s INSIDE"
-->
PTt
(
"play table tennis inside"
)
-->
heparin
(
"Hep is in the liver"
)
-->
slower
(~ 5 min.)
--> Intrinsic pathway is INDEPENDENT
of where the blood is and SLOWER
--> i.e: the instrinsic pathway happens with blood
even in a test tube, independent of being in body
Cofactors 8 and 5:
note tat factors 8 and 5 are cofactors
they don't "activate" other factors
they combine with other factors
the brackets in 10 = (5) x 2 x 1 means that
--> 10 and 5 combine to make 2
same with cofactor +8
--> the brackets tells us that (8) is at the end of intrinsic pathway, but it is added to 9 to activate factor 10
*Blood Transfusions
Hypocalcemia
from high volume blood trasnfusions
Notes
:
note that blood transfusion have citrate added into them
--> citrate is an anticoagulant
citrate then metabolized to sodium bicarbonate in the liver
too much citrate chelates Ca++ in particular
leads to hypocalcemia
--> mostly parasthesias in the limbs
Clinical Cases
Clinical Case
Clinical Case
Notes
:
note that
*Home
*Polycythemia = Erythrocytosis
high Hematocrit = RBC volume/total plasma volume
true vs relative polycythemia
--> true = RBC actual volume is larger
--> relative = plasma volume down = diuretics usually
primary vs secondary polycythemia
--> primary = high RBC volume made in the primary spot = bone marrow / low EPO response
--> secondary = not large enough RBC volume from external = secondary cause / high EPO trying to respond
Clinical Cases
Clinical Case
Notes
:
note that
Clinical Case
*Polycythemia Vera
"VERY large RBC polycythemia"
polycythemia vera has true = large RBC volume and low EPO response
*EPO and darbopoetin
note CKD patients often have ACD = anemia of chronic disease
Tx = EPO or darbopoetin
--> they can increase the RBCs two much
--> cause HTN and cardiac problems from thick blood
*mixed Platelet and Coagulation disorders
Von Willebrand disease
--> vW disease most common inherited bleeding disorder
--> but is very mild
DIC = Disseminated Intravascular Coagulation
*DIC = Disseminated Intravascular Coagulation
a common complication of sepsis in which you have widespread and systemic (hence Disseminated)
--> activation of BOTH internal and external coagulation pathways
--> use up all clotting factors
--> longer PTT and PT
Result = excessive bleeding from loss of all clotting factors
presents POST sepsis
--> excessive epistaxis (nose bleeding)
--> bleeding from venupuncture sites of inserted needles or catheders
*Bleeding time
pricked 3-4 mm deep and see how long it takes to form a clot
--> normal time should be about 2-5 min.
Clinical Cases
Clinical Case
Clinical Case
Notes
:
note that
*Von Willebrand disease
vW disease most common inherited bleeding disorder
--> but is very mild
*Bleeding time
pricked 3-4 mm deep and see how long it takes to form a clot
--> normal time should be about 2-5 min.
*PT and PTT
PT = Prothrombin Time
--> measures the extrinsic system as well as
--> plus factors common to both systems and
PTT = Partial Thromboplastin Time
--> measures the intrinsic system and the common components
